DNA sequence represents a single format upon which a broad range of biological phenomena (e.g. genetic variation, RNA expression, protein-DNA interactions, chromosome conformation, etc.) can be evaluated for high-throughput data collection. Over the past three years, massively parallel DNA sequencing platforms have become widely available, reducing the cost of DNA sequencing by over two orders of magnitude, and essentially putting the sequencing capacity of a major genome center in the hands of investigators with access to a single such instrument. The widespread application of these technologies has the potential to dramatically accelerate genomics-driven research. We are a group of eleven faculty investigators from three departments (Genome Sciences, Pathology, and Medicine) at the University of Washington (UW), who seek to extend their currently funded research in human and model organism genetics, population genetics, pharmacogenetics, and systems biology, with this request for a single next-generation sequencer to be operated as a shared resource as a part of a sequencing cost center. Specifically, funds are requested to acquire an Illumina Genome Analyzer II ("GA-II") platform, equipped with a paired-end module. The instrument can produce more than ~2.5 gigabases per instrument-run, split across up to 8 libraries, at a rate of 1 Gigabase per day and for reagent costs of less than $5 per megabase. Lastly, this instrument will benefit from significant institutional commitment and local expertise in DNA sequencing production and data analysis.